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蛋白激酶C对自发性高血压大鼠肥大心肌细胞无负荷收缩功能的调节

王云英, 余志斌

第四军医大学航空航天生理学教研室.陕西,西安 710032

摘要

在慢性压力超负荷引起心肌肥大过程中，蛋白激酶C (protein kinase C, PKC)的激活起关键性作用，激活的PKC也能调节心肌收缩性能。该文旨在研究自发性高血压大鼠(spontaneously hypertensive rats, SHR)心肌肥大的不同阶段PKC调节心肌收缩性能的特征。采用胶原酶法分离4月龄与10月龄Wistar--Kyoto (WKY)、SHR大鼠的心肌细胞，观测单个心肌细胞无负荷缩短幅值以及在PKC激动剂与抑制剂作用下心肌收缩性能的变化。结果表明：刺激频率从1 Hz增至3 Hz，WKY大鼠心肌细胞无负荷缩短幅值逐渐增加，呈正阶梯效应；4月龄SHR大鼠心肌细胞的缩短幅值较WKY大鼠增强，但在各刺激频率下其缩短幅值基本保持不变；10月龄SHR大鼠心肌细胞的缩短幅值在1 Hz下与WKY大鼠无差别，随刺激频率增加，收缩幅值降低，呈负阶梯效应。PKC激动剂PMA灌流条件下，50、100与200 mmol/L的PMA分别降低WKY大鼠心肌细胞缩短幅值至(69.8±1.9)% ({sl P}<0.01)、(58.2±2.2)% ({sl P}<0.01)与(22.7±2.5)% ({sl P}<0.01)，呈浓度依赖关系；4月龄SHR大鼠心肌细胞缩短幅值的降低更明显，分别降至(6.1±0.7)% ({sl P}<0.01)、(2.4±0.2)% ({sl P}<0.01)与(12.5±2.6)% ({sl P}<0.01)；PMA降低10月龄SHR大鼠心肌细胞缩短幅值至(65.7±1.6)% ({sl P}<0.01)、(53.9±4.0)% ({sl P}<0.01)与(16.3±2.0)% ({sl P}<0.01)，小于对4月龄SHR大鼠心肌细胞缩短幅值的作用。PKC抑制剂staurosporine增加WKY大鼠心肌细胞缩短幅值，200 nmol/L的staurosporine灌流条件下，WKY大鼠心肌细胞缩短幅值增加(63.63±4.53)% ({sl P}<0.05)，4月龄SHR大鼠心肌细胞缩短幅值增加(80.82±4.61)% ({sl P}<0.05)，10月龄SHR大鼠心肌细胞缩短幅值增加(80.97±4.59)% ({sl P}<0.05)。结果提示，在SHR大鼠心肌肥大初期，具有负性肌力作用的PKC异构体可能被激活，并参与对心肌收缩性能的调节；而心肌肥大稳定阶段，这些PKC活性可能恢复至正常水平。

关键词： 心肌肥大; 蛋白激酶C; 心肌细胞; 缩短幅值

Protein kinase C regulates unloading contraction of cardiomyocytes in hypertrophic heart of spontaneously hypertensive rat

Wang Yunying, Yu Zhibin

Department of Aerospace Physiology, the Fourth Military Medical University.Xi'an 710032,Shaanxi

Abstract

The activation of protein kinase C (PKC) is not only a pivotal node during cardiac hypertrophy in chronic pressure-overloadedheart, but also involved in the regulation of cardiac contractility. The aim of this paper was to observe PKC modulation in cardiaccontractility at different stages of cardiac hypertrophy in spontaneously hypertensive rat (SHR). The cardiomyocytes were isolatedfrom 4- and 10-month-old normotensive Wistar-Kyoto (WKY) and SHR rat hearts. The shortening amplitude of unloading contractionin cardiomyocytes was observed by an Edge Detector system. The shortening amplitude in WKY rat cardiomyocytes increased graduallyas the stimulating frequency increased from 1 to 3 Hz. The shortening amplitude was positively correlated with stimulating frequency.The shortening amplitude in 4-month-old SHR group was enhanced as compared with that in WKY group at the same stimulatingfrequency. When the stimulating frequency increased, the shortening amplitude did not increase in 4-month-old SHR group. There wasno difference in shortening amplitude between 10-month-old SHR and WKY groups at 1-Hz stimulating frequency. But the shorteningamplitude in 10-month-old SHR group decreased when the stimulating frequency increased to 3 Hz. The perfusion of 50, 100 or 200nmol/L PMA (a non-specific agonist of PKCs) significantly reduced the shortening amplitude in WKY and SHR groups. The shorteningamplitude was reduced to (69.8±1.9)%, (58.23±2.2)% and (22.73±2.5)% (all P

Key words: cardiac hypertrophy;Protein kinase C;Cardiomyocyte;shortening amplitude

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引用本文：

王云英, 余志斌. 蛋白激酶C对自发性高血压大鼠肥大心肌细胞无负荷收缩功能的调节[J]. 生理学报 2008; 60 (2): 197-204.

Wang Yunying, Yu Zhibin. Protein kinase C regulates unloading contraction of cardiomyocytes in hypertrophic heart of spontaneously hypertensive rat. Acta Physiol Sin 2008; 60 (2): 197-204 (in Chinese with English abstract).